Distinct Roles of Myosins in Aspergillus fumigatus Hyphal Growth and Pathogenesis

Abstract

cMyosins are a family of actin-based motor proteins found in many organisms and are categorized into classes based on their structures. Class II and V myosins are known to be important for critical cellular processes, including cytokinesis, endocytosis, exocytosis, and organelle trafficking, in the model fungi Saccharomyces cerevisiae and Aspergillus nidulans. However, the roles of myosins in the growth and virulence of the pathogen Aspergillus fumigatus are unknown. We constructed single-and doubledeletion strains of the class II and class V myosins in A. fumigatus and found that while the class II myosin (myoB) is dispensable for growth, the class V myosin (myoE) is required for proper hyphal extension; deletion of myoE resulted in hyperbranching and loss of hyphal polarity. Both myoB and myoE are necessary for proper septation, conidiation, and conidial germination, but only myoB is required for conidial viability. Infection with the ⌬myoE strain in the invertebrate Galleria mellonella model and also in a persistently immunosuppressed murine model of invasive aspergillosis resulted in hypovirulence, while analysis of bronchoalveolar lavage fluid revealed that tumor necrosis factor alpha (TNF-␣) release and cellular infiltration were similar compared to those of the wild-type strain. The ⌬myoE strain showed fungal growth in the murine lung, while the ⌬myoB strain exhibited little fungal burden, most likely due to the reduced conidial viability. These results show, for the first time, the important role these cytoskeletal components play in the growth of and disease caused by a known pathogen, prompting future studies to understand their regulation and potential targeting for novel antifungal therapies.

Disruption of actin motor function due to MoMyo5 mutation impairs host penetration and pathogenicity in Magnaporthe oryzae

“…As the class V myosin acts as a vesicle transporter to the hyphal tip (Desnos et al ., ; Hammer and Sellers, ; Taheri‐Talesh et al ., ), the loss of MoMyo5 may disturb the correct trafficking of components required for hyphal extension, thus causing abnormal hyphal branching. Our results are consistent with previous findings indicating that A. fumigatus MyoE is required for normal septation, but not septal morphology (Renshaw et al ., ).…”

“…The Δ Momyo5 mutant forms appressorium‐like structures on hyphal tips as normal, but does not successfully infect host cells, indicating that MoMyo5 is dispensable for the formation of appressorium‐like structures, but is critical for pathogenesis. Previous studies in A. fumigatus and U. maydis have revealed that the Δ AfmyoE mutant completely lacks conidia when cultured in glucose minimal medium (GMM) and exhibits attenuated virulence, and Δ Ummyo5 exhibits defects in the early infection in planta (Renshaw et al ., ; Weber et al ., ). Our findings are consistent in that MoMyo5 is equally important in asexual development and pathogenicity.…”

“…Nevertheless, significant defects were found. In A. nidulans and A. fumigatus, deletion and conditional depletion of MyoE caused hyperbranching, loss of hyphal polarity and a noticeable reduction in colony size (Renshaw et al, 2016;Taheri-Talesh et al, 2012;Zhang et al, 2011b). In C. albicans and U. maydis, the mutation of class V myosin led to significant attenuation in filament formation (Weber et al, 2003;Woo et al, 2003).…”

“…Unlike budding yeasts, polarized growth is a continuous and indefinite process in filamentous fungi which requires both microtubules and actin filament-mediated transport of cargoes to the hyphal tip (Fischer et al, 2008;Zhang et al, 2011b). In Aspergillus fumigatus and Candida albicans, AfMyoE is required for hyphal extension, conidial germination, chitin distribution and virulence, and CaMyo2 is essential for polarized growth and hyphal transition (Renshaw et al, 2016;Woo et al, 2003). In Ustilago maydis, UmMyo5 plays an important role in the mediation of mating, hyphal growth and pathogenicity (Weber et al, 2003).…”

The Myosin5‐mediated actomyosin motility system is required for Verticillium pathogenesis of cotton

“…Myosin V participates in exocytosis and organelle transport, including cellular transport of secretory vesicles (Jin et al, 2011;Hammer and Sellers, 2012;Taheri-Talesh et al, 2012), peroxisomes (Fagarasanu et al, 2009), mitochondria (Altmann et al, 2008) and the endoplasmic reticulum (Estrada et al, 2003). Myosin V was also found to be critical for maintaining polar growth and virulence of the human pathogen Aspergillus fumigatus (Renshaw et al, 2016). In Ustilago maydis and Magnaporthe oryzae, deletion of the class V myosin reduced virulence against maize and rice plants, respectively (Weber et al, 2003;Tang et al, 2018).…”